The primary objective of this Mentored Patient-Oriented Research Career Development Award is to permit Rebecca M. Evans (the candidate) to develop her full potential as a clinical investigator in dementia research. Dr Evans has completed a 2-year fellowship in neurodegenerative disease and has initiated research into vascular aspects of dementia. She has been, and will continue to be actively involved in the hands-on examination of participants in the Indianapolis-Ibadan Dementia Study (IIDS), a cross-cultural, longitudinal, population-based study of dementia in elderly Africans and African Americans. As the APOE epsilon 4 allele is not associated with AD risk in blacks, Dr Evans' initial research project will focus on examining three candidate genes for AD risk. Given that hypertension is very prevalent in the black population, and is a major vascular risk factor, and the emerging recognition that vascular factors increase AD risk, the genetic polymorphisms chosen to study for AD risk are all associated with hypertension in blacks. Dr. Evans will study the angtiotensin I converting enzyme (ACE) gene insertion/deletion polymorphism, the angiotensinogen allele T235, and epithelial sodium channel variants for association with Alzheimer's disease (AD) in each cohort of the IIDS. During the award period, she will work with her mentors to design and implement preliminary case control studies to assess the significance of vascular risk factors in AD patients and patients with post-stroke dementia. Dr. Evans' future goal is to obtain independent grant funding to develop and implement 1.) larger studies of vascular risk factors for AD, and 2.) interventional trials of therapy to modify vascular risk factors which might prevent or delay dementia onset or slow disease progression. Didactic courses are planned in epidemiology, clinical trial design, statistical analysis, and the ethical conduct of research. This career enhancement plan will enable Dr. Evans to develop expertise in patient-oriented research, and help her accomplish her goal of becoming an independent investigator.